Antacid composition containing hydrated magnesium aluminate



United States Patent 3,323,993 ANT/\Cll) COMPOSITION CONTAINING HY-DRAIEE) MAGNESIUM ALUMINATE Remsen Ten Eyck Schenck, Bangor, Pa.,assignor to Keystone Chemurgic Corporation, Bethlehem, Pa., acorporation of Pennsylvania No Drawing. Original application Sept. 29,1960, Ser. No. 59,155. Divided and this application Oct. 29, 1963, Ser.No. 319,644

3 Claims. (Cl. 167-55) The present invention relates to a new chemicalcom pound consisting of hydrated magnesium aluminate, and processes forits production.

This application is a division of my copending application Serial No.59,155, filed September 29, l960, now abandoned, which application was acontinuation-in-part of my then copending application Serial No.839,303, filed September ll, 1959, and now abandoned, which applicationwas a continuationdn-part application of my then Copending applicationSerial No. 647,448, filed March 21, 1957, and now abandoned.

The anhydrous form of magnesium aluminate,

is exemplified by the well-known mineral spine]. It has also beensynthesized by heating at a very high temperature a mixture of magnesiumand aluminum oxides. I11 this state, it is comparatively inert towardnearly all chemical reagents, and possesses a high fusing point.Particularly well-crystallized specimens are valued as gemstones; exceptfor this and some limited use as a refractory, the substance is oflittle interest chemically and of none at all biologically.

It has also been proposed to produce metal aluminates by reacting analkali metal aluminate and a salt of a metal. Reactions of this sort aredescribed in US. Patents 2.395.931, and 2,413,184 and result in productswhich are relatively inactive chemically and which have substantiallylower water contents and greater particle size characteristics than theproduct of the present invention.

I have now discovered that magnesium aluminates may be economicallyprepared in a hithcrto-undescribed, high ly hydrated and chemicallyactive form. When produced by one of the wet processes hereinafterdescribed, hydrated magnesium aluminate is a finely-divided, tasteless,insoluble white powder which, in contrast to the magnesium aluminateproducts hitherto known is highly re active toward many chemicalreagents, notably toward acids.

A suspension of the hydrated magnesium aluminate of the presentinvention in distilled water shows a pH of 8.0 to 8.5. On addition ofdilute acid, such as N/lO HCl, the first action involves decompositionof the molecule into aluminum hydroxide and magnesium chloride. Thelatter dissolves, while the former remains suspended in a very highlyactive form. Two equivalents of acid are consumed in this step, and thepH drops to approximately 4. Further additions of acid to the mixturereact with the liberated aluminum hydroxide. This step takes place at aconstant pH; no reduction of pH below 4 can occur until all the aluminumhydroxide is consumed. Since six additional equivalents of acid arerequired for this, the buffer action of the hydrated magnesium aluminateof the present invention in the region of pH. 4 is pronounced.

By virtue of the above properties, the hydrated magnesium alnminate ofthe present invention is of interest pharmacologically, as a treatmentfor excessive gastric acidity. Unlike many other remedies of this type,it cannot over-alkalize the gastric juice when used in normal or usualdoses. It establishes a pH in the ideal range near 4 in the stomach, andmaintains this for an extended pe- 3,323,993 Patented June 6, 1967 riodin spite of continual secretion of additional acid by the stomach.

The term hydrated magnesium aluminatc as used throughout thisspecification and in the appended claims is intended to designate theproduct of the present invention, as produced by the processes hereindisclosed and which is characterized by a water content of from to 66%.

The hydrated magnesium aluminate of this invention is devoid oftoxicity, its metabolic products being simple magnesium and aluminumsalts, and may thus be freely ingested; the dosage required is smallbecause of its low equivalent weight. In spite of the relatively highdegree of hydration of the salt, the equivalent weight is only 40, whichis comparable with those of calcium carbonate and magnesium carbonate,and less than half as great as that of sodium bicarbonate.

Hydrated magnesium aluminate contains no carbon dioxide, and this is nota carminative. In some applications this is a decided benefit, as forinstance where a simple antacid effect, unaccompanied by eructation, isdesired.

Few side-effects. and those of no importance, have been reported toaccompany the use of aluminum and magnesium compounds as antacids. Theformer occasionally produces a slight tendency to constipation, whilethe latter sometimes has a laxative action. Neither effect isappreciable in normal dosage. Furthermore, it is believed that combiningthe two substances in a singie treatment, as in hydrated magnesiumaluminatc, results in cancellation of the two factors.

Hydrated magnesium aluminate may profitably be used as an additionalingredient in pharmaceutical formulations designed primarily for otherpurposes than control of gas tric acidity. For example, certainsubstances widely employed as analgesics have, as a side-effect, theproperty of irritating the gastric mucosa into secreting more than thenormal amount of acid. The hydrated magnesium aluminates of the presentinvention may be advantageously incorporated with such analgesics.

I have discovered two processes for producing a pure hydrated magnesiumaluminate in finely divided form and having a water content of from 50%to The first of these processes consists in adding an alkali metalaluminate solution to a solution of a magnesium salt and simultaneouslyadding an acid at a rate such that the pH remains within a range inwhich the upper limit is the pH at which magnesium hydroxide canprecipitate and the lower limit is the pH at which aluminum hydroxideprecipitates more rapidly than magnesium aluminate is formed. This rangeis from pH 6 at the lower limit to pH 10 at the upper limit.

The second process consists in first preparing a slurry of basicaluminum magnesium carbonate in water, and then boiling this slurry. Inthe boiling the carbonate is hydrolyzed and carbon dioxide is liberated.When no further carbon dioxide can be driven oil by continued boiling,the residual insoluble salt consists of hydrated magnesium aluminate.

The processes referred to above for preparing hydrated magnesiumaluminate are illustrated in more specific detail in the followingexamples:

Example L-In a reaction vessel equipped with a mo chanical stirrer,means for adding simultaneously two separate liquids at individuallycontrolled rates, and a set of electrodes for determination of the pH ofthe mixture, is placed a solution of gms. of magnesium chloride in 1liter of water. A quantity of sodium illuminate containing 0.4gram-atoms of aluminum, corresponding to 33 gm. of actual NaAlO isdissolved in 2 to 4 times its own weight of water to make a fairlyconcentrated solution, and this is allowed to tlow slowly into thestirred magnesium solution. The pH of the mixture. which is close to 7initially, begins to increase as aluminate solution is added. When itreaches 8, the simultaneous addition of dilute hydrochloric acid(conveniently of about 10% strength) is commenced. The flow of bothsodium aluminate and hydrochloric acid solutions is so regulatedthroughout that the pH of the reaction mixture is maintained between 8and 9. When all the aluminate solution has been added. the flow of acidis likewise terminated. The final reaction mixture should have a pH of 8to 9. The precipitate is collected by filtration or centrifugation,adherent mother liquor being displaced by a brief washing of the cakewith water. By drying and grinding the resulting magma. there isobtained approximately 60 gm. of a finely-divided white powder which israpidly and completely soluble in dilute acids. A typical analysis ofthis product is:

Algog, 31.7%

MgO. 12.4%

which corresponds to the formula MgAl O (OH) .8H O. or MgO.Al O .10H O.The water content is thus about 56%, and this figure should bemaintained within the range of about 50-60% water in order to obtain theactive hydrated magnesium aluminate of the present invention. In therange from about 50-60% water, the formula for the hydrated magnesiumaluminate of the present invention covers the range from MgO.Al O .8H Oto Example 2.In a reaction vessel equipped with a mechanical stirrer, ameans for heating the contents, a gas inlet and dispersion tube, a meansfor adding liquid at a controlled rate, and a set of electrodes fordetermination of the pH of the mixture. is placed a solution of 75 gm.of magnesium chloride in 1 liter of water. With the stirrer in vigorousoperation, a steady stream of carbon dioxide is allowed to flow into thesolution through the gas dispersion tube. A quantity of sodium aluminatecontaining 0.4 gram-atoms of aluminum. corresponding to 33 gm. of actualNaAlO is dissolved in 2 to 4 times its own weight of water to make afairly concentrated solution, and this is allowed to flow slowly intothe stirred, carbonated magnesium chloride solution at such a rate as tokeep the mixture vcry faintly basic. preferably at a pH between 7 and 9.When all the sodium aluminate solution has been added. the flow ofcarbon dioxide is stopped and the precipitate is separated as completelyas possible. by filtration or centrifugation, from the mother liquor.The cake is returned to the reactor and redispersed in 1 liter of freshwater. Heat is applied to the resulting slurry, and the suspension isboiled until carbon dioxide is no longer evolved. It is then againfiltered or centrifugated and the resulting magma is then dried andfinely ground. The product is similar in all respects to that obtainedin Example 1.

Example 3.Aluminum hydroxide gel is prepared, by known methods leadingto a product of highest activity, as a paste containing approximately10% of A1 by weight. A quantity of. this paste corresponding to 0.4gram-atoms of aluminum (204 gm. of gel) is added to 1.1 liters of anaqueous solution of magnesium bicarbonate of 0.2 molar concentration.and the mixture is stirred until a uniform dispersion is obtained. Thisis introduced into a pressure vessel equipped with a stirrer, a gasinlet tube, and a means for heating the contents. Under continuousstirring, the air in the reactor is replaced by an atmosphere of carbondioxide; the vessel is then sealed and additional carbon dioxide isadmitted to a pressure of 1 to 3 atmospheres. When equilibrium has beenestablished and gas is no longer absorbed by the contents of thereactor, the carbon dioxide supply line is shut off and heat is appliedto the vessel. The tempera ture is maintained, with uninterruptedstirring, between 50 and 100 C. for several hours; at the end of thistime the reaction mixture is cooled, the pressure is released,

and the precipitate is separated from the mother liquor by filtration orcentrifugation. The cake is resuspended in about 1 liter of fresh water,and the resulting slurry is gently boiled until carbon dioxide is nolonger evolved. The magma is again dcwatercd; on drying and grinding ityields a product similar in all respects to that described in Example 1.

Example 4.-in a reaction vessel equipped with a mechanical stirrer. agas inlet and dispersion tube, and a means for adding liquid at acontrolled rate, is placed 1.] liters of an aqueous solution ofmagnesium bicarbonate of 0.2 molar concentration. With the stirrer invigorous operation, a steady stream of carbon dioxide is allowed to flowinto the solution through the gas dispersion tube. To this stirred.carbonated magnesium solution there is slowly added, at a rate such thatlocal excesses are avoided and thorough mixing is promptly achieved. 82gm. (0.4 moles) of liquid aluminum isopropoxide. either as thesupercooled molten form or as a solution in a minimum of warm absoluteisopropyl alcohol. The mixture is stirred for a few minutes afteraddition is complete, and the precipitated product is collected byfiltration, centrifugation or decantation. The cake, freed as completelyas possible from mother liquor. is resuspended in about 1 liter of freshwater and the slurry is gently boiled until carbon dioxide is no longerevolved. The resulting magma is then dewatered; upon drying and grindingit afiords a product similar in ail respects to that obtained in Example1.

Example 5.ln a reaction vessel equipped with a mechanical stirrer, meansfor adding simultaneously two separate liquids at individuallycontrolled rates, and a set of electrodes for determination of the pH ofthe mixture, is placed a solution of 75 gms. of magnesium chloride in 1liter of water. A quantity of sodium aluminate containing 0.4 gram-atomsof aluminum, corresponding to 33 gm. of actual NaAlO is dissolved in 2to 4 times its own weight of water to make a fairly concentratedsolution. and this is allowed to flow slowly into the stirred magnesiumsolution. The pH of the mixture which is close to 7 initially, begins toincrease as aluminate solution is added. When it reaches 8, thesimultaneous addition of dilute acetic acid (conveniently of about 10%strength) is commenced. The flow of both sodium aluminate and aceticacid solutions is so regulated throughout that the pH of the reactionmixture is maintained between 8 and 9. When all the aluminate solutionhas been added, the flow of acid is likewise terminated. The finalreaction mixture should have a pH of 8 to 9. The precipitate iscollected by filtration or centrifugation, adherent mother liquor beingdisplaced by a brief Washing of the cake with Water. By drying andgrinding the cake, there is obtained approximately 60 gm. of afinely-divided white powder which is rapidly and completely soluble indilute acids.

While I have described the present invention in terms of preferredexamples, it will be understood that various modifications andsupplemental steps may be employed in carrying out the process asdefined in the appended claims. For instance in the step of regulatingthe pH by addition of dilute acid, other common acids may be substitutedfor those described: any acid which forms a soluble salt with magnesiummay be chosen. Furthermore, both the magnesium salt and the alkali metalaluminate may be dissolved in water to give solutions of concentrationswidely diflerent from the specific examples cited. Likewise, the alkalimetal aluminate may be the aluminate of lithium, sodium, potassium,rubidium, or cesium. although the sodium or potassium aluminate ispreferred as being more readily available. The proportions of magnesiumand aluminum taken may be stoichiometrically exact, or the magnesium maybe taken in excess over a Wide range.

For use as an antacid, the hydrated magnesium aluminatc of thisinvention is preferably tabletted in unit doses 5 containingapproximately 5 grains of the active ingredient per tablet. Sugar,dextrin or other binder can be used in the tabletting operation.

For the treatment of gastric hyperacidity, these tablets are taken bymouth. A single S-grain dose is nearly always suflicient to affordprompt relief. If distress recurs, the dose may be repeated. Followingtreatment with the product of the present invention, the duration ofeffective gastric acidity control is more prolonged than that attainedwith products that do cause acid rebound.

Having thus described my invention, I claim:

1. An essentially non-systemic anti-acid composition prepared in unitdosage quantity for combatting excessive gastric acidity, comprising abinder and hydrated magnesium auminate characterized by the formulawherein the water content is in the range of from about 50% by weight toabout 60% by weight, and wherein x is an integer from 8 to 12 inclusive,said hydrated magnesium aluminnate being soluble in dilute acids.

2. An essentially non-systemic anti-acid composition prepared in unitdosage quantity for combatting excessive gastric acidity, comprising abinder and hydrated magnesium aluminate characterized by the formulasaid composition of matter being soluble in dilute acids.

3. The composition in accordance with claim 1, each unit dosage quantitycontaining approximately 5 grains of said hydrated magnesium aluminate.

References Cited UNITED STATES PATENTS 2,269,508 1/ 1942 Barton 23-522,413,184 12/1946 La Lande 2352 2,880,248 6/1959 Paterson 167-552,940,898 6/1960 Denison 167-55 3,066,073 11/1962 Ratclitf 167-553,156,615 11/1964 Denison 16755 ALBERT T. MEYERS, Primary Examiner.

SAM ROSEN, JULIAN S. LEVITT, Examiners.

1. AN ESSENTIALLY NON-SYSTEMIC ANTI-ACID COMPOSITION PREPARED IN UNITDOSAGE QUANTITY FOR COMBATING EXCESSIVE GASTRIC ACIDITY, COMPRISING ABINDER AND HYDRATED MAGNESIUM AUMINATE CHARACTERIZED BY THE FORMULA